Toward Outcome Measurement of Anxiety in Youth with Autism Spectrum Disorders

描述（由申请人提供）：这个为期四年的多地点项目将在未来的自闭症谱系障碍（ASD）青年临床试验中推进焦虑的结果测量。项目公告（PAR-11-045）宣布，缺乏发育障碍人群的结局指标是发育障碍人群药物研究的主要障碍。损害性焦虑在患有ASD的年轻人中很常见，并且是一个合理的治疗目标，但研究不足（白色等人，2009;货车斯滕塞尔等人，2011年;国王 例如，2009年）的报告。在典型发育中的青少年中，存在广泛接受的焦虑结果测量（RUPP Anxiety Group，2001; Walkup等人，2008年）。考虑到自闭症儿童的语言和认知缺陷，这些措施不适合自闭症儿童。消费者团体也注意到了对自闭症青年焦虑的结果测量的必要性（www. autismspeaks.org）。我们已经组建了一支由研究人员和顾问组成的优秀团队，开发了一种父母评级和临床医生评级的工具，用于测量参与临床试验的ASD青少年的焦虑。我们提出了一种符合FDA专著《患者报告的结局指标：用于医疗产品开发以支持标签声明》（www.Fda.Gov/Cder /Guidance）的混合方法。在第一年，与父母的焦点小组将探讨自闭症儿童焦虑的表现。这些信息将用于完善CASI焦虑量表（基于DSM-IV的父母评级），并修改临床医生评定的儿科焦虑评定量表（PARS）。第2年将在一个安全的网站上收集900名5至17岁ASD儿童的修订后CASI Anx量表（20-25项）数据。本研究将探讨此量表的分布、内部一致性、因素结构与项目分析。量表的重测信度将在在线的子样本中进行评估。 受访者和亲自评估的受试者样本。将通过对比与另一种父母评定的焦虑测量（收敛效度）以及与重复行为、社交障碍和易怒测量（发散效度）的相关性，评价CASI Anx量表的有效性。将通过对90名受试者的亲自评估收集修订后的PARS，以评价第3年的可靠性（评估者间、内部一致性）和有效性。在第34年，将在心率[HR]、心率变异性[HRV]和皮肤电活动[EDA]的生理指标方面，比较高度焦虑亚组（高于CASI Anx量表阈值）与对照组（轻度焦虑ASD）。将在静息和轻度焦虑激发条件下测量HR、HRV和EDA。这项探索性研究的结果可能会识别出用于ASD焦虑化合物早期测试的读数。该项目有四个可交付成果：焦点小组结果（第2年）;一个可靠和有效的家长评定的焦虑结果测量（第3年）;一个可靠和有效的临床医生评定的焦虑测量（第4年）;初步HRV和EDA结果（赠款期后不久）。 公共卫生相关性：自闭症谱系障碍（ASD）是一种致残性疾病，估计每1000名儿童中有9名（约45万名5至17岁的美国儿童）受到影响。至少有三分之一（15万）的自闭症青少年因焦虑问题而进一步残疾。该项目的重点是自闭症青年焦虑的结果测量，这是推进药物和心理社会治疗的先决条件。

DESCRIPTION (provided by applicant): This four-year multisite project will advance outcome measurement of anxiety in future clinical trials in youth with autism spectrum disorders (ASDs). Program announcement (PAR-11-045) declares that the dearth of outcome measures in developmentally disabled populations is a major impediment for drug research in developmentally disabled populations. Impairing anxiety is common in youth with ASDs and a plausible treatment target, but poorly studied (White et al., 2009; van Steensel et al., 2011; King et al., 2009). There are well-accepted outcome measures for anxiety in typically developing youth (RUPP Anxiety Group, 2001; Walkup et al., 2008). Given the language and cognitive deficits in ASDs, these measures are not suitable for youth with ASDs without modification. The need for outcome measures for anxiety in youth with ASDs has also been noted by consumer groups (www. autismspeaks.org). We have assembled an outstanding team of investigators and consultants to develop a parent-rated and a clinician-rated instrument for measuring anxiety in youth with ASDs who participate in clinical trials. We propose a mixed method approach in line with the FDA monograph: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims (www.Fda.Gov/Cder /Guidance). In Yr 1, focus groups with parents will explore the manifestations of anxiety in children with ASDs. This information will be used to refine the CASI Anxiety scale (DSM-IV-based parent-rating) and modify the clinician-rated Pediatric Anxiety Rating Scale (PARS). Yr 2 will collect data on the revised CASI Anx scale (20-25 items) in 900 children with ASD ages 5 to 17 years on a secure web site. We will examine the distribution, internal consistency, factor structure and item analysis of this parent-rated scale. Test-retest reliability of the scale will be evaluated in a subsample of online respondents and a sample of subjects assessed in person. Validity of the CASI Anx scale will be evaluated by contrasting the correlations with another parent-rated measure of anxiety (convergent validity) and with measures of repetitive behavior, social disability and irritability (divergent validity). The revised PARS will be collected via in person assessments of 90 subjects to evaluate reliability (inter-rater, internal consistency) and validity in Yr 3. In Yrs 34, a high anxiety subgroup (above threshold on the CASI Anx scale) will be compared to controls (ASD with low anxiety) on physiological measures of heart rate [HR], heart rate variability [HRV] and electrodermal activity [EDA]). HR, HRV and EDA will be measured at rest and under mildly anxiety provoking conditions. Results from this exploratory investigation may identify read outs for early testing of compounds for anxiety in ASDs. The project has four deliverables: focus group results (Yr 2); a reliable and valid parent-rated anxiety outcome measure (Yr 3); a reliable and valid clinician-rated anxiety measure (Yr 4); preliminary HRV and EDA findings (soon after the grant period). PUBLIC HEALTH RELEVANCE: Autism Spectrum Disorders (ASDs) are disabling conditions affecting an estimated 9 per 1000 children (roughly 450,000 American children between age 5 and 17 years). At least a third (150,000) of youth with ASDs is further disabled by anxiety problems. This project is focused on outcome measurement of anxiety in youth with ASDs, which is a prerequisite for advancing drug and psychosocial treatments.